Chen Gang, Xu Litao, Ye Guanxiong, Lin Junhua, Meng Zhiqiang, Shen Yehua
Department of Pediatric Cardiothoracic Surgery, Children's Hospital of Fudan University, Shanghai, People's Republic of China.
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
Onco Targets Ther. 2021 Jan 5;13:13451-13463. doi: 10.2147/OTT.S282350. eCollection 2020.
Pancreatic cancer is one of the most lethal malignancies. Accumulating evidence supports for the critical contribution of long noncoding RNAs (lncRNAs) to the cancer development and progression. We tried to identify novel lncRNAs involved in the pancreatic carcinogenesis.
Two independent datasets (Gene Expression Omnibus datasets: GSE16515 and GSE32688) were obtained from the Gene Expression Omnibus (GEO). The level of BC037916 was detected in pancreatic cancer tissues and adjacent no-tumorous tissues (n=86) by qRT-PCR. Effects of BC037916 on proliferation, apoptosis, and invasion of pancreatic cancer cells were examined.
We identified a novel lncRNA BC037916 involved in the pancreatic carcinogenesis by analyzing GEO datasets. Quantitative RT-PCR analysis showed that 86.0% (74/86) pancreatic cancer tissues had increased BC037916 expression as compared with normal counterparts. Further, positive correlation was observed between BC037916 expression and clinical stage, primary tumor, and regional lymph node invasion. Importantly, BC037916 was an independent prognostic factor of pancreatic cancer. Functionally, knockdown of BC037916 repressed cell proliferation, inhibited cell invasion, halted cell cycle progression, and promoted apoptosis in both PANC-1 and SW1990 cells. In contrast, overexpression of BC037916 in CAPAN-1 had opposite effects. Moreover, silencing of BC037916 significantly inhibited the tumor growth of xenografted SW1990 cells in vivo. Results of Western blot assays suggested that BC037916 knockdown also suppressed the activation of JAK2/STAT3 and TGF-β signaling. Further experiments suggested that BC037916 positively regulated the expression of Twist through miR-3145-3p.
BC037916 exhibited oncogenic potential in pancreatic cancer development.
胰腺癌是最致命的恶性肿瘤之一。越来越多的证据支持长链非编码RNA（lncRNAs）对癌症发生和发展的关键作用。我们试图鉴定参与胰腺癌发生的新型lncRNAs。
从基因表达综合数据库（Gene Expression Omnibus，GEO）获得两个独立的数据集（GEO数据集：GSE16515和GSE32688）。通过qRT-PCR检测86例胰腺癌组织及癌旁非肿瘤组织中BC037916的水平。检测BC037916对胰腺癌细胞增殖、凋亡和侵袭的影响。
通过分析GEO数据集，我们鉴定出一种参与胰腺癌发生的新型lncRNA BC037916。定量RT-PCR分析显示，与正常组织相比，86.0%（74/86）的胰腺癌组织中BC037916表达增加。此外，BC037916表达与临床分期、原发肿瘤及区域淋巴结浸润呈正相关。重要的是，BC037916是胰腺癌的独立预后因素。在功能上，敲低BC037916可抑制PANC-1和SW1990细胞的增殖，抑制细胞侵袭，阻止细胞周期进程，并促进细胞凋亡。相反，在CAPAN-1中过表达BC037916则产生相反的效果。此外，沉默BC037916可显著抑制体内异种移植的SW1990细胞的肿瘤生长。蛋白质印迹分析结果表明，敲低BC037916也可抑制JAK2/STAT3和TGF-β信号通路的激活。进一步实验表明，BC037916通过miR-3145-3p正向调节Twist的表达。
BC037916在胰腺癌发生发展中具有致癌潜能。
